Synthesis of 4-hydroxy-2-cyclo-penten-1-ones



clwn n ial Patented Dec. 1, 1953 SYNTHESIS OF 4-HYDROXY-2-CYCLO- PENTEN-l-ONES Milton S. Scheehter, Washington, D. (7., and Frederick B. La Forge, North Arlington, Va., dedicated to the free use of the People of the United States No Drawing. Application February 8, 1949, Serial No. 75,282

(Granted under Title 2365,;)U. S. Code (1952),

19 Claims.

sec.

This application is made under the act of March 3, 1883. .As amended by the act of April 30, 1928, and the invention herein described, if patented in any country, may be manufactured and used by or for the Government of the United States of America for governmental purposes throughout the world without the payment to us of any royalty thereon.

We hereby dedicate the invention herein described to the free use of the people in the territory of the United States to take eifect on the granting of a patent to us.

Since the publication of the results of the investigations of Staudinger and Ruzicka on the active principles of pyrethrum flowers [Helv. Chim. Acta, 7, 177-259, 377458 (1924)], considerable work was done to revise and correct the structures which they proposed. The present invention relates to the synthesis of esters closely related to the pyrethrins and having their characteristic insecticidal properties. This invention also relates to the synthesis of cyclopentenolones and to hydroxydiketones which can be cyclized to cyclopentenolones. some of these new cyclopentenolones are comparable or superior to the pyrethrins and cinerins in insecticidal activity. I. I V

The hydroxydiketones prepared according to duced by the cyclization of the hydroxydiketones.

B may be a hydrocarbon radical or substituted hydrocarbon radical such as alkyl, fore'xainpl'e',

methyl, ethyl, propyl, iso-propyl, n-butyl, secondary butyl, tertiary butyl, n-amyl, secondary and tertiary amyl, n-hexyl and isomers, heptyl, octyl, nonyl, dodecyl, octadecyl, and substituted alkyl, alkenyl such as allyl, 2-methylallyl, vinyl, and 2- or 3-butenyl, substituted alkenyl such as 2- or 3-chlorallyl, alkynyl such as 2-propynyl, alkadienyl, such as 2, 4-pentadienyl, alkatrienyl. aryl such as phenyl and napthyl, alkylaryl such as xylyl, aralkyl such as benzyl and phenylethyl, aralkenyl such as cinnamyl, cycloalkyl such as cyclopropyl, cyclohexyl and cyclopentyl, and cycloalkenyl such as cyclopentadienyl or cyclohexenyl. R mayalso be a heterocyolic radical such as furfuryl or thenyl.

Certain esters of B may be alkyl such as methyl, ethyl, propyl, iso-propyl, butyl, secondary and tertiary butyl, pentyl and isomers, octyl, decyl, and heptadecyl, substituted alkyl, alkenyl or substituted alkenyl,

aryl such as phenyl, methyl phenyl, Xylyl, sub-' Formula I c n O Formula II Formula IV any compound of the type Rj- -CQ-CHO, Formula IV.

The reactants for preparing the hydroxydi ketones arethe alkali salts 'of betaketo acids of the typeR,QI-I2 IQO CI-Iz -CQO M (Formula III) and the substituted glyoxals of the type 3 R 'COCHO (Formula IV). The substituted glyoxals may be prepared by many different methods known to those skilled in the art, one such convenient method being the oxidation of methyl ketones, R- CO-CHs, or aldehydes having an alpha methylene group,

by selenium dioxide. Thus, acetone may be oxidized to pyruvaldliyde, ECHa -eCGV-"QGHOfand acetophenoneto phenyl'glyoxal, CsH5 -CO- CI-IO. The alkali salts of beta-keto acids may be pre-.

pared by saponification of the corresponding beta-keto esters at room temperature '.or lowerrzrs imetalflandstheicarbon dioxide resulting from the by means of aqueous solutions of alkali hydroxam ides. Any excess alkali left. at the end ofithe. saponification may be neutralized.witlilacidiora by bubbling carbon dioxidedintd'thellsolufiion- A. Certain beta-keto acids which are sufficiently stable, such as beta-oxocaprylic acid, may be isolated as such, stored at low temperature and neutralized with cold aqueous alkali when ready tobe used.

The synthesis of compounds of the type shown 5 in Formula I consists in reactirig'pinsubstan-itially equi-molecular quantities, at room temperature or below, a substituted glyoxal of the type shown-in For-mula l v 'with a bet'a-keto acid or the typeshown in Fo'fmula III lvl hydro'geni 3 or with one of itsi-"alkalisalts 1 (Formula l 1' M sodiu'm" or potassiumlil-the I pit- 6f the solu tiori=preferably. beinawkept between rabout pH 5 to =aboiit pH-9l It is inadvisabl to have -the v solution too alkalin'epr too acidicIi If'it is too alkaline some of the substituted glydxal may rearrange to a hydroxyacidgawhereas if it is too acidic, some of the beta-keto acid may decompose; in either case, the' yields of desired product will be lowered: To' maintain the pH with- 40 in desired limits, thereaction may be carried out in the presence of buffers, or else acid or alkali may be added as'the reaction proceeds. The substituted glyoxal may be-used pure or in solution. If the substituted glyoxal is only moderately soluble in water, such as phenylglyoxal, the reaction mixture may be agitated or a cosolvent such as alcoholamayebe added. Provided that the solution is not made-too acidic nor too alkaline at first, the pH will teridto adjust itself to a suitable valu because'zof the production of alkali bicarbonate, the reaction probably taking place by the mechanism :shown in Equation 1, where M is an alkali :metal suehras Na or K.

Equation 1.

[IV-C 0OHOH-JH-C O UH -RJ, (Intermediate condensatlon product) l'i'HaO Secondly, when the reaction is run under alkaline conditions, the hydroxydiketone may be extracted directly from the reaction mixture which is still faintly alkaline at the end of the reaction. Thirdly, when the reaction is run under alkaline conditions, after having extracted the hydroxydiketone, a titration of the remaining extracted liquid for alkali bicarbonate indicates that practically the theoretical amount is produced.

If, by means of buffers or by the addition of acid,'the?reaction is runiunder acidicrfcond-itions, the" formation of the intermediate condensation product takes place as shown in Equation 1,

where M is now hydrogen rather than an alkali decarboxylation of the intermediate condensationproduct is liberated as a gas instead of appea/ring as alkali/bicarbonate.

The mechanismsproposed above are not to be consideredeas limitin'g' the invention in any way since the reactionsmay actually take place in a difierentmanner;

Thereactions are usually substantially complete dnrabout six hours at room temperature but may be allowed to proceed for a longer period. Thehydroxydiketones may be separated from the" reaction mixtures, dried, and distilled in vacuo, or they may be extracted with a solvent such as 'ether. The-ether solution is then-Washed, dried,= and the' ether evaporated, the residue be-' mg: subjected todistil1ation'=-'inhigh vacuum. The yields usuallyare from about 50% to of the theory." 1- Whereas :We' prefe'r aqueous or aqueous-alcoholicsolutionsfit is within the scope'of this invention :to carry rout the"preparation "of the hydroxydikestones in organic "solvents. specific'examples of the preparation of hydroxydikestones of the type illustrated in Formula I will'xbe described-in the experimental'section. I

The cyclopentenolones-are prepared by the cyclization of the'hydroxydike'stones in a suitable alkalinetmedium. Wheh the"hydroxydikestones are rtreated with aqueous 'or aqueous-alcoholic" solutions. of "alkaline cyclizing' agents'such' as sodium hydroxide; pOtassium hydroxide, barium hydroxide; 1 pipridih'e-'-or quaternary ammonium hydroxides, water is eliminated intramole'cularlv and" the" hydroxydikestones are-converted to cyclopentenolones asshown=inEquation 2; The employmentpf'mto "20"volumes of a l to "10%"? aqueous sodium hydrdxide solution has 'proved to be *quitesatisfactory; Althoughit is preferable' to use 'thdistilld'hydroxydik'etones;it is possible '-to "employ" the "crudei undistille'd (prod ucts. Whereas we prefer aqueousior aqueous al coholicsolutions; it is withinrthe' SCOpe 'Of this. invention to carry 'out the cyclizations' in "organic; solvents;

Th' ibeta iketv estersdistd in -rwa51er below were-prepared employing the-"general procedures described by" soloway'and Iia' Forged. chem; i Soc;69; 2677 Yl94'77fGreen and'La'For'ge, J. Am.

Chem. Soc. 70, 2287 (1948),- and Wallingford, Homey'er andJones, J. Am. Chem. Soc, 63, 2252 (1941), except for methyl 3-oxo-7-octenoate, which was prepared by the method of Harper, J. Chem. Soc., 892 (1946).

Several beta-keto acids were prepared by saponification of the corresponding esters with a slight excess of a 5 to aqueous potassium hydroxide solution at about 5 for three days. Upon acidification to Congo red with dilute sulfuric or hydrochloric acid, the free keto acids were obtained. Beta-'oxocaprylic acid, M. P. 75-76 (dec.) [0. f. Locquin, Bull. Soc. Chim. 31 (3), 597- (1904) and 3-oxo-6-octenoic acid, M. P. 71 -72 (dec.), were thus prepared. These acids are stable for months in the refrigerator but slowlydecompose at room temperature with the liberation of carbon dioxide. 3-oxo-6-heptenoic acid was prepared in the same manner but was isolated as an oil which crystallizes on cooling with Dry Ice and melts on warming to room temperature with slow decomposition.

Pyruvaldehyde was prepared from acetone and selenium dioxide by the general procedure of Riley and co-workers [J Chem. Soc. 1875 (1932) 621 (1938)]. Phenylglyoxal hydrate was prepared according to Organic Synthesis, Collective vol. II, p. 509 (1943), John Wiley and Sons, Inc., New York, N. Y. The pyruvaldehyde was assayed by the methods of Friedemann, J. Biol. Chem. 73, 331 (1927) and Simon and Neuberg, Biochem. Zeit., 232, 4'79 (1931) The procedures used by us in the preparation of the hydroxydiketones of Formula I are as follows:

Procedure A.The beta-keto acid was isolated as described above, mixed with ice-cold water and exactly neutralized with cold 10% sodium hydroxide solution. The pyruvaldehyde, usually dissolved in a little Water, was added and the al kalinity adjusted to approximately pH 8. It is immaterial if the pyruvaldehyde has polymerized during storage in the refrigerator since it either dissociates on standing in dilute aqueous solution or else a shift of equilibrium to the monomer occurs as it reacts. When phenylglyoxal hydrate, which is not very soluble in water, was employed, the reaction mixture was shaken or stirred.

If the reaction medium is too alkaline, some of the substituted glyoxal may be converted to a hydroxy acid before it can react with the salt of the beta-keto acid. In those cases where the hydroxydiketones are insoluble, the reaction mixture turns cloudy in about two hours and the oily reaction product separates practically comusually a fraction, not further investigated, havs. ing a considerably higher boiling point than the desired compound. v

Procedure B.-This isthe same as procedure A exceptthat the beta-keto ester was saponified with a slight excess of a 5 to potassium hydroxide'solution for several days in the refriger- 6 ator. The excess alkali was neutralized with dilute sulfuric acid, the substituted glyoxal added, and the alkalinity adjusted to approximately pH 8.

Procedure C'.This is the same as procedure B" except that instead of neutralizing the alkaline solution of the beta-keto acid with dilute sulfuric acid, the solution was saturated with carbon dioxide using a porous disperser. The excess alkali is thereby converted to bicarbonate giving a suitable pH and the substituted glyoxal may be added without further adjustment of the alkalinity.

A number of hydroxydiketones of the type illustrated in Formula I, were prepared by these general procedures. Table II sets forth a number of hydroxydiketones prepared by one of procedures A, B, or C, and the reaction conditions, and physical constants of the hydroxydiketones. Table III presents the analytical data on the hydroxydiketones and their semicarbazone derivatives (prepared in pyridine-ethanol solution). The analyses of the semicarbazone derivatives indicated that water had been eliminated so that they are either anhydrodisemicarbazones or pyrazoline' derivatives. The anhydrodisemicarbazones can be obtained in lowand high-melting forms depending on the solvent used for recrystallization.

Typical experiments describing the preparation of hydroxydiketones and some variations which may be employed follow:

3-hydroxy-2,5decanedione (Table II, compound A) .Procedure A was used. Thirty grams ofbeta-oxocaprylic acid (0.19 mole) mixed with 50 ml. of cold water in a glass stoppered flask was kept cold in an ice bath and titrated with 10% sodium hydroxide solution until just a1- kaline to phenolphthalein. The stoppered flask was shaken vigorously near the end of the titration. Eighteen grams of pyruvaldehyde (87.6% assay) (0.22 mole) was added and rinsed in with a little water. The alkalinity of the reaction mixture was adjusted to approximately pH 8 using a pH test paper, by the careful addition of a little 10% sodium hydroxide solution. The total volume of the reaction mixture was 200 ml. In about two hours at room temperature, the solution turned milky and the oily reaction product which was forming rose to the surface. After two days, the reaction mixture was still faintly alkaline. It was extracted several times with ether, the extracts were combined and washed several times with saturated sodium chloride so lution and after drying the extract over anhydrous sodium sulfate, the ether was distilled off leaving a residue of 32 g. of yellow oil which was distilled in vacuo. After a small forerun, the main fraction was collected at 89-95" (0.05 mm), most of it distilling at 9395, 11 1.4514; yield 23 g. (65%). There was also a higher boiling fraction, B. P. -155 at 0.15 mm., which was not investigated.

An aliquot of the reaction mixture, after it had been extracted by ether, was titrated for sodium bicarbonate using 1 N sulfuric acid solution and with beta-oxocaprylic acid and pure pyruvalde- (instead of hydra-sodium bisulfite compound pyruvaldehyde) with final adjustment of the alkalinity to approximately pH 8. After standing for two days, very little oil separated. The re-' action: mixture; was acidifiedeto .Congo red with'ldilute sulfuric. acid (1 4). :andheated .for '15 .min.;

on-thesteam bathiunder. a refluxcondenser in.-.

order to decompose any bisulfite addition com-.-

pounds....-The..product. was isolated :as ,usual by extraction withether and distillationin vacuo, i.

solution but it was noted that-it contained form? I aldehyde, acidic substances, and other unknown I impurities. Procedure 13 was used; Ninety-nine grams. (0.53 mole) of ethyl beta-oxocaprylate was mixed with 195 -ml.. of an ice-cold solution containing 39 g. of'pota-ssiumhydroxide (86% assay) (0.60 mole). After standingfor three days in therefrigerator, the excess alkali was approximately neutralized by the slowaddition of dilute sulfuricuacid (11 1). One hundred and forty grams of commercial pyruvaldehyde (0.58 mole) was added and the. solutionaadjustedtoapproximately pH 7.5-8 by the addition of 10% potassium hydroxide solution; .The total..- volume of the reaction mixture was53'7 ml. In

ninetyminutes, the reaction: product began -to separate as an oil whichfloated to the surface. After four hours, 104 ml. had separated after whichthere was no further increase. The next day, the product was isolated in the usual manner by extraction with ether and distillation to yield, after a small forerun, 50.9 g. (52%) B. P. 105-410 at'OA mm n 1.4532. Redistillation gave 41.7 g., B. P. 90-98 at 0.05 mm n 1.4528.

To illustrate that the reaction can be run under acidic conditions, a solution .of -sodium betaoxocaprylate (0.05 mole) was reacted withpyruvaldehydein the presence of a buffer consist- 3-oxo fi-heptenoic acid and pyruvaldehyde (see Table II, compound C) it was also prepared using pyruvaldehyde diethyl acetal asa source of pyruvaldehyde.

Seventeen: and a half grams..(0.12 mole) .of

pyruvaldehyde diethyl .acetal was-refluxedfor one hour with 1.6 g. of concentrated sulfuric acid in m1. of water. Thesolution was cooled in anice bath and neutralized by the slow addition of about 3 g. of sodium. bicarbonate. was used. Starting with 17 g. (0.10 mole) of ethyl -60 Procedure C 3-oxo-6-heptenoate, saponified at 5 for'several days with 'll g. of potassium hydroxide (87.5% assay) (0.11 mole) in 80 m1..of water, and. the

hydrolyzed pyruvaldehyde diethyl. acetal solution,

the reactiontime being two days, .10.6 g. (62% yield) .of distilled productwas obtained, 12.

Treatment of the. hydroxydiketoneswith acetic anhydride and anhydrous sodium-acetate led to... the .formation of anhydrocompounds of the typer illustrated in Formula IV. The. disemicarbazones. ofthese seemto beiidentical with the anhydrodisemicarbazones of the corresponding hydroxy-.

8 Qn s as :proved bystheir analyses and mixed -i melting .points. ,fIhei analyticaldata ontthe" hydrocompounds and theindisemicarbazones. are presentedin Table-IV...

Theanhydrocompounds prepared were 3-dec" ene-2,5'-dione; 3;8 decad1ene-2,5 dione; '3,8 nona-' diene=2,5-dione; 3,9=-decadiene-2,5-.dione; fro'nri. the corresponding hydroxydiketones'.

Th'e'procedure for cyclizin'g the hydroxydik'e tones ,to cyclopentenolones is as follows. The'hy' j droxydiketone'was placed in a glass-stopperedEr lenmeyer flask or bottle and 10 to 20vo1umes of If to 10% sodium hydrdx'rde "solution was. added: Although'other alkaline'cyclizmg agents 'suchias potassium hydroxideibarium hydroxide, quatera 1' nary ammoniumhydroxides; and 'piperidini can; be used, sodium "hydroxide wastfou'nd to giveiunif formly goody'ield "andwas generallyfbmployedr; The air" was" displaced. with nitrdg'e'ni'and the' slightly lubricatedstopperinserted. If i'urther i precautions against oxidation "are desired, boiled. I, water maybe used in making"up:th'alkalhsolue'.- tion, and a smallamount of hydroquinone may be added to i the reaction. mixture. It 'T'was thh. shaken for oneto four hours on'a shaking ma-I, chine, occasionally somewhat longer. The, reaction mixture turns .yellow' as soon -as .th. alkali is added and usually becomes-darker as there-.- action proceedsrrAftei extraction with peroxide-J free ether (inthe OaS."0f .thelower. molecular' weight 'cyclopentenolones, .after saturationv .with salt) theextract was washed several time withli. saturated salt solution and after drying. over sodium sulfate, the "solvent was-removed and the..- residue distilled in high, vacuum. sometimes. there was a smalllfor'e'run (probably"uncyclized hydroxydiketone) ;1 In'each ease,v asin the disea. tillation. of .the' hydroxydiketones, .therelwas a. fraction; not further investigated, boilir'igconsiderably higher than the desired..compound.,

Table JV "presents .-the' cyclopentenolones of For'mulalI which were preparedt 'Th'ecompound 3-hydroxy-2,5 hexanediohe, .Heiizes ketol (Table. f II, 'compoundH) 'dould .'riot belcycliz'e'd byalkali; I it yielded; instead; a complexmixturebf prod-.1. ucts. The; analytical dataon; the cyclopens tenolones and their semicarbazones are-presented in Table "VII cyclopentenolonesarelthe dl or racemic compounds.Whidhmaybe-resolvdJay conventional means to "yield-"the .optically'iactive d and 1 forms. a

MIWOoZ-OB-O condoned Boiling point mmmwmmm sesame Yield Grams of Percent i'ound Time, hours Analysis 050 mmwmamm Percent calculated Percent assay Anhydrodisemicarbazone Formula TABLE 11 Formula I ABCDEFO r-petroleum ether).

M. P., C. cor.

b 224-225 GrzHzzOzNa b 227228 5 228-229 b 225-226 CuHzoOzNe 220-221 5 214-215 b 238-239 Starting ester I Pyruvaldehyde Grams Table I Grams found Hydrozydiketones of i the time illustrated in P 1'0 ce dure AAAOOOBO TABLE III Percent Analysis where procedure A was used, the weight refers to the beta-keto acid, not the ester.

Percent calculated Product, Formula I ound could be crystallized, M. P. 38.539 (ethe Hydroxydiketones and their anhydrodisemicarbazones Formula This comp I See Table I for the esters b Phenylglyoxal hydrate.

d Ethyl acetate.

- Product was extracted with other in a continuous extractor from the sodium chloride-saturated reaction mixture.

Compound I Disemicarbazone, M. P., "O. cor.

b 231-232 6 228-229 b 220-221 d 214-2l5 0, 51. at; H, 7.94.

Percent found Analysis eulated Percent calposition. mposition.

Formula position. 7.86. Found: tic acid melts with decomposition.

mpounds. etic acid ethanol, melts with decom Compound, Formula V -I1-C4Hs CHzCH=GHCHa CH3CH=OH2 CHzOHzOH=CHz stallized from 95% Anal; Calculated for CuHnOzNo: C d Recrystallized from ace 8 See Table II for the co b Recrystallized from ac s Recrystallized from 95% ethane a Recrystailized from petroleum ether. b Recry crystallized in refrigerator, melts on warming.

nan tone used I used Product, Formula II hours Distilled product imt, Yie1d Boiling point 1 Pini Grams of theory i I... ,,.Z See Table II for the hydroxydiketones used. b Regeneration from thcsemicarbazoneEan The hydroxydiketone dissolved in a swept flask.

d Regenera ddistillat ionigavem produ little ethanol was slowly dropped into the alkali with stirring in a nitrogen tion from the semicarba zoneand distillation gatespi'ohiit, When regenerated fromthe'semicarbazonethis'compoundcrystaliized,

B. aim-114 10.51 'niih. ,'h; 9 1.5120.

M. T. 97. 54815 (benzenemetroleum ether) Percent calculate'd pound P ercent iound.

Formula Analysis Percent cal- V Percent culated foun i "C E asses; .e ssese.

1 See Table V for the compounds.

b Recrystallized from methanolethyl acetate, mel Analysis on the compound regenerated from its se 4 Percent nitrogen.

I Analysis on crystalline compound, see Table V, footnote a Recrystallized from acetic acid, melts with decomposition.

The synthetic 2 2 butenyD-4-hy methyl 2 oyclopenten 1 -"c' rie'(For'rhiila'II have prepared is not identical T; 1th fiatiifal fdlj cinerolone which has been ass gned tli'fefsame structural formula [La Forgefand- Soloway, J.. Am. Chem. Soc. 69, 2932 (1947)]. The mi ppear to be cis-trans or geometrical isomers. .lVIixtures of corresponding derivatives shbw definite melting-point depressions. Howevew ofn' hyidifogenation, both of these cyclopentenoloiiesyield the identical product, dl-dihydrojqinro'lorie.

All of the substituted cycl 'periteriolones described herein in Table V haye...hcen, est-erified with natural d-trans-chrysanthemum monocarboxylic acid yielding esters analogous to cinerin I. In addition, two of them, Formula II, R.=--CH.-a, R:CH2CH=CHCH3 and Formula II, R=-CH3, R:-CH2CH=CH2, have each been esterified with synthetic dl-cisand ditrans chrysanthemum monocarboxylic acids. These esters were prepared by mixing a benzene solution of the crysanthemum monocarboxylic acid chloride with a benzene solution of the cyclopentenolone containing a slight molecular excess of pyridine. After one day, ether was added and 75 ts with decomposition..- i

micarbazone and distilled.

"the etlffs'olutidh was washeasut'cessivei with watrfdiliiteacidfdiliitesod'iiim'bicarbonatesolution,fand then with saturated sodium chloride "solution. After drying the ether solutiomthesolwent wasremov diin vacuum leaving the ester.

Table VII containsdata on the toxicity of some *festers of the new cyolopehtenolones to houseiflies and Tables VIII and IX give data on aerosol terminations containing the d-trans-chrys'an- I I: "lcfoxylicacid ester"oi"2-allyl=4'- liydroxy-3-metliyl- 2f-cyc 'penteii-l on'e 1('ste'r A "of Tables 'VI'I'I'ari'd ixrafid the ii-traris-clirys anthemum monocarboikylic acid ester of dliydroxyi3 methyl 2 (2; methylallyl) 2 cyclopenten-l-one (ester of Tables VIII andJlQ Injaddition to the estelrs slfiow n in l able VII, '2 'fallyl 4 E liy Q' eyho- H 4 drsx .zap-irithyr-= penten- 1-one -has-beerresteriiied in thesaifie way with the following acids (via the acid chlorides) 2-(1-methy1vinyl) cyclopropanecarboxylic acid.

2 methyl 2 (1 methylvinyl)cyclopropanecarboxylic acid.

3 isobutyl 2,2-dimethylcyclopropanecarboxylic acid.

2 methyl 2 (3 methyl 3 butenyDoyclopropanecarboxylic acid.

, 2,2 dimethyl 3 (1 methylpropenyDcyclopropanecarboxylic acid. I (ll-Chrysanthemum monocarboxylic acid, synthetic cis-trans mixture.

All of these esters exhibited toxicity and knockdown to houseflies.

The synthetic estershave certain advantages over pyrethrum extract, such as freedom from irritating impurities and freedom from insoluble impurities which cause clogging difficulties in I formulations used for aerosol-type insecticides.

TABLE'VII Toxicity of cyclopentenolone esters to houseflies O 010- Ooncen- Knockpeliteno- Acid used to prepare tration down 25 jg g lone ester 01' ester-. minutes, in 1 da used I mgJrnl. percent y A Natural d-trans-chrys- 32 100 so antheimuniidmonocar- 1g I 22 boxy ac 4 g 2 B 1 100 37 1 it i; 0. 0 0. 25 100 44 r 2 a a 1 0.5 100 48 2 2 do N 1 98 16 16 2i 8 F 4 97 27 8 188 it 4 G 2 9s B dl-Cis-chrysanthemum 2 88 40 monocarboxylic acid. 2 100 28 2 is s 1 0 0. 5 r 0 3 dl-Trans-ehrysanthe- 8 0 B mum monocarboxylic 4 100 54 acid. 2 .100 29 2 a s V n 1 H '0 "do n at 71 Standard-natural pyrethrins in g 55 refined kerosene. 0 92 100 24; 29; 33

Y e Table V (or the eyclopentenolones of Formula II used.

l he solvent was refined kerosene and tests were made by the turntable method [Campbell and Sullivan, Soap 14 (6): 119 (1938)] TABLE VIlI Tests of aerosol formulations (m hoaseflies at a dosage of 4.63 0/1000 cu. ft., average of 4 tests J t? Concenown Percent sample Material tretion, mmmutes killin N0 percent 1 day 1 esse; Ester! }81 e5 99 79 I I, a 1 v V V o-5s1. {Ester '10 51v so 93' .4

t" a time; I?

G rum (34583-- Mattias chloride 6 at as so 49 Freon-12 89 I Pyrethrins 1%.

{3, 14 TABLE IX Tests of aerosol formulations on houseflies at a dosage of 1.16 g./1000 cu. ,ft., average of 3 tests lmPergcgnt Concenown Percent 11? Material tration, m mmutes killin percent lday 0.4 3 o-ssvu g 61 72 85 9a 0.4 L b i1 2 u rica mgo yre rins ur e 0.

- DDT 3 (Fr-586.. g 16 '37 52 88 G-179 Lubricating oil 5 20 44 61 93 Oyclohexanone. 5 Freon12 85 e 2% of a 20% pyrethrum extract was used.

Although the primary object of this invention is the preparation of esters of synthetic cyclopentenolones having a high order of insecticidal toxicity and knockdown, it is within the scope of this invention to prepare esters of the new cyclopentenolones using acid anhydrides or acid chlorides of other acids such as formic, acetic, propionic, palmitic, stearic or other fatty acids, unsaturated aliphatic acids such as aleic acid,'saturated or unsaturated cyclic or polycyclic acids, aromatic acids such as benzoic acid, substituted aromatic acids, heterocyclic acids, or substituted heterocyclic acids. The new cyclopentenolones and their esters are potentially useful as intermediates in the preparation of other compounds and in the preparation ofinsecticides, perfumes, detergents and wetting agents.

Cross-reference is made to our continuationin-part application Serial No. 161,481, filed on May 11, 1950, to the cyclopentenolone esters and divisional application's'erial No. 168,142, filed on June 14, 1950, directed to the hydroxydiketones. Having thus described our invention, we claim: 1. A method of preparing a cyclopentenolone of the formula:

comprising treating ahydroxydiketorie of the formula:

a spondingtoithe formula:

. ,the. semicarbazone of which. melts with decom means methyl-Z-cyclopenteri- =ne comprising treating t e compound or theifa mn with an alkaline cyclizing agent.

42 A process of preparing 4-hydroxy-3+methylwith, an alkaline cyclizing agent; the process .abeing carriedouttin the substantial absence, of

y .air,.. the alkaline, cyclizing agent, being .aqueous z-("2 -methylallyl) -2=cyclopenten-1=one"compris sodium hydroxideing treating thecompound of the formula g I 1 g OH; H

with an alkaline cyclizinggagent.

5i A: process For preparing- -2 -'-(12+buteny1) -4- hydroxy-3z-m'ethyl 2 cyclopenten-i one, correpositioniat about'222 -Z-223 0;, comprisin treating cyclizing agent.

ten-Leone.

7-: 4=hydroxy 3 s"methyl zflkmethylallyl)- 2 cyclopenten-1 -one.

8. Syntheic racemic 2-'(2+butenyly-4'ahydroxy- 3-'methy1 2 4 .cyclopenten-i-one;;the;isemicar=r 'bazone'of which hasamemngpointwim decompositioniatabout222%223"C.

9-. 2-(3- buteny1) 4 f'j-,.hydroxy ,1-" 3 '-,m"ethyI*2- cyclopentenel one.

butenyl) 27-cyclopenteIi-1-'one. ""11; 2aallyls4=hydroxy-3rphenyl zcyciopenten- @112: A- methodptiipreparin ai-tcyclopentenolone --orthe formula:

7 1 271 EO rGH: a.) 2

15. Amethod of preparing avcyclopentenolone .'ofrthe formula:

comprising treating aaqhydroxydiketone oi! the formula: R'COCHOHCH2CO--CH2R with :an alkaline cyclizing agent) R: being-taken from the group consisting of alkyl, alkenyl-and .haryl radicals, Rheing a hydrocarbon radicalrhav- 16; A:'4 hydroxyccyclopentenone of theigroup consisting-of-2-allyl- 4 hydroxy 3 --methyl-2- cyclopenten 1 one; 4-.-hydroxy 3 '-!methy11(2- methylallyl) 2 e cyclopentenl one; synthetic racemic 2-(2 butenyl) 4 hydroxy-3i-methylt z-cyclopenten-l-one,s'the-semicarbazonefor-Which has a :meltingpoint with decompositionjat about 222-223 C.; 2--(3-butenyl)-4-hydroxy-3-methy1- 2-cyc1openten-1-one;; 4-hydroxy-3-methyl-2- (3- l allyl-4#hydroxy-B-phenyl-2-cyc1openten-l-one.

17. A method of preparing a cyclopentenolone of theiormula:

riLLo H comprising treating i a -hydroxydiietone of the r; formula: R'-CO-,CHOHCHz--=CO-CHzR with tan; alakline cyclizing. agent, Rf; being taken from the group-consisting of alkyl, alkenyl and 1 aryl radicals, Rbeing a hydrocarbon. radical hav- 'ing at least one olefinic bond, the process being carriedvout in a non-oxidizing atmosphere.

a18i'5The, process or, claimi 12 in ,whichrthe' proc- -"---ess is carried out at ordinary room temperature.

19. The process of claim 14 in which the process is carried out at ordinary room temperature.

MILTON S. SCHECHTER. FREDERICKZ'BLLA FORGE.

8x32 gffggig gfififififigf fifig References Cited inthe' file or this parent with an alkaline cyclizing agent, R being taken 1 UNITED STATES PATENTS whom the group:consistingaof alkyl,z alkenyland S'Number Date aryl radicals, B being taken from the group-con: 096 1 Oct 5264,1937 sistmg alkyl'alkenylsubstitutedalkenyl' and? 2:387:58? iI-Iunsdiecker Oct. 23 1945 aralkyl, cycloalkyl and. cycloalkenyl radicals, the reprocessheing carriedgputiinfiinerh atmosphere.

1 13;;The processor :olaimA-12inzwhichithecyclizzingiagentaisc aqueousisodiumzhydroxide.

" OTHER REFERENGIEZS La-Forge and solowayz J;hml cthem". =Soc.;ivo1. 69, page 186, (January-i947). Crombie et a1.:

$141344: prm':essi'roriipreparing"-2allyl-4 l'1ydroxy- 5 Nature, .vo1.:"162, pages 222 223 (1948) 

1. A METHOD OF PREPARING A CYCLOPENTENOLONE OF THE FORMULA:
 16. A 4-HYDROXY CYCLOPENTENONE OF THE GROUP CONSISTING OF 2-ALLYL - 4- HYDROXY - 3 - METHYL-2CYCLOPENTEN - 1 - ONE; 4-HYDROXY - 3 - METHYL-(2METHYLALLYL) - 2 - CYCLOPENTEN-1-ONE; SYNTHETIC RACEMIC 2-(2 - BUTENYL) - 4 - HYDROXY-3-METHYL2-CYCLOPENTEN-1-ONE, THE SEMICARBAZONE OF WHICH HAS A MELTING POINT WITH DECOMPOSITION AT ABOUT 222-223* C.; 2-(3-BUTENYL)-4-HYDROXY-3-METHYL2-CYCLOPENTEN-1-ONE; 4-HYDROXY-3-METHYL-2-(3METHYL-2-BUTENYL)-2-CYCLOPENTEN-1-ONE; AND 2ALLYL-4-HYDROXY-3-PHENYL-2-CYCLOPENTEN-1-ONE. 